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Description of key information

The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats (reference 7.2.1-1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2021-01-26 to 2021-03-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 17, 2001
Deviations:
yes
Remarks:
Please refer to "Principles of method if other than guideline".
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
yes
Remarks:
Please refer to "Principles of method if other than guideline".
Principles of method if other than guideline:
The relative humidity varied from 26.5 – 55.0 %. Therefore, the relative humidity was transiently outside the guideline range of 30 - 70 %. This minor transient deviation did not influence the integrity or outcome of the study.
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 9 weeks
- Weight at study initiation: 167 g (range from 151 to 177 g)
- Fasting period before study: yes. Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Housing: group-housed before treatment (type IV Makrolon® cages), single after treatment (type III Makrolon® cages), group-housed starting 1 day after treatment; on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria) with play tunnels (Ref. 14153, Plexx BV, Netherlands)
- Diet: ad libitum; with fasting before treatment; maintenance diet (VI534, ssniff Spezialdiaten GmbH, Germany)
- Water: ad libitum; community water
- Acclimation period: at least 5 days
- Microbiological status when known: not specified; The health status of the rats was checked upon arrival and immediately before start of the experimental phase.
- Method of randomisation in assigning animals to test and control groups: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 - 23.3
- Humidity (%): 26.5 - 55.0
- Air changes (per hr): not specified; fully air-conditioned room
- Photoperiod (hrs dark / hrs light): not specified
Route of administration:
oral: gavage
Vehicle:
other: 0.25 % aqueous hydroxypropylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 g/L
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: A well-tolerated and established standard vehicle was used.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

CLASS METHOD
- Rationale for the selection of the starting dose: The toxic potential of the test item could not be estimated Therefore, the study was started in 3 females with 300 mg/kg.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of treatment, each animal was observed for mortality and for symptoms of intoxication for at least 6 hours after administration. On the following days, the rats were examined once daily. All animals were weighed before treatment (day 1) and on day 2, 4, 6, 8, 11, 13 and 15. The animals treated with 2000 mg/kg were additionally weight on day 3.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes
Statistics:
No statistical analysis was conducted.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
The body weight gain of three animals treated with 2000 mg/kg bw on day 2 was lower compared to all other rats. The body weight development of all other rats was inconspicuous throughout the study.
Gross pathology:
No organ alterations were identified during the gross pathological examination.
Other findings:
No other findings observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.
Executive summary:

A study according to OECD TG 423 was conducted to identify potential toxic effects of the test item, after single oral administration to rats in a stepwise procedure. The study was started with 300 mg/kg bw in 3 female rats, continued with further 3 females treated with 300 mg/kg bw. Due to the fact, that no mortality was seen after treatment with 300 mg/kg bw, further 6 females were treated with 2000 mg/kg bw. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight gain on day 2 of three rats treated with 2000 mg/kg bw was lower compared to all other rats. The body weight development of all other rats was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
A GLP and guideline conform study was conducted and is considered of sufficient quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity


A study according to OECD TG 423 was conducted to identify potential toxic effects of the test item, after single oral administration to rats in a stepwise procedure. The study was started with 300 mg/kg bw in 3 female rats, continued with further 3 females treated with 300 mg/kg bw. Due to the fact, that no mortality was seen after treatment with 300 mg/kg bw, further 6 females were treated with 2000 mg/kg bw. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight gain on day 2 of three rats treated with 2000 mg/kg bw was lower compared to all other rats. The body weight development of all other rats was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. The test item has no acute toxic potential under the conditions of the present study, and the LD50 value is higher than 2000 mg/kg after single oral administration in female rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.
As a result the substance is considered to be not classified for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the fifteenth time in Regulation (EU) No 2020/1182.